Entry of the HIV virus in cells involves several viral proteins including the envelope proteins gp41 and gp120. The first step of the replication cycle of the HIV virus involves the binding of the virus to auxiliary T4 lymphocytes by interaction of the gp120 protein with the CD4 cell protein. Further, in order that the fusion of the viral and cell membranes occurs, the HIV virus has to interact with a cell co-receptor. The most important co-receptors in vivo are the receptors of chemokines CXCR4 and CCR5. The use of the different co-receptors is associated with the time-dependent change in the immune deficiency and therefore to the infection: at the beginning of the infection, so-called R5 viruses interact with the CCR5 co-receptor and then at a later stage, certain viruses (so-called X4 viruses) use the CXCR4 co-receptor. At this stage, the viral population either comprises a mixture of R5 and X4 viruses, or viruses with double R5/X4 tropism. In certain cases, the viruses R5 may directly induce the occurrence of AIDS, however it is the occurrence of X4 viruses which is generally associated with the development of the disease. It is therefore essential to be able to detect early the occurrence of X4 viruses in the patient.
Thus, a certain number of methods having the purpose of determining cell tropism of HIV viruses have been developed.
For example, the TROFILE test (MONOGRAM) is a phenotype test of the HIV virus proposed by Monogram Biosciences and Pfizer. First of all, a library of vectors containing the regions coding for the envelope of HIV viruses of a patient is elaborated. These vectors are then amplified and the regions coding for the envelope are cloned in a vector expressing a HIV virus without any envelope protein and expressing the gene of luciferase. Finally, the recombinant viruses obtained from these vectors are used for infecting cells expressing CD4 and CCR5 or CXCR4. The virus capacity of infecting these cells is determined by measuring the light emission produced by luciferase. This test has several drawbacks, as notified in November 2007 by the TRT-5 to the Afssaps (French Agency for the Safety of Health Products) and the HAS (<<Haute Autorité de la Santé>>, French National Authority for Health). First of all it has a very high cost. Further, the time for receiving the results is from four to five weeks, which is not compatible with fast decision-making in the case of a change of treatment. Further, it is not impossible that a change in viral tropism may occur in certain patients within such a time. Moreover, no profile test is available for viruses of the HIV-2 types.
Therefore, there exists a real need for simple, fast, reliable and inexpensive alternative tests allowing determination of the cell tropism of HIV viruses. The object of the present invention is to provide such tests.